Effects of growth factors and hormones on growth and morphological differentiation of human breast epithelial cells within collagen gel in serum-free medium.

When human epithelial cells that had grown out from either carcinoma or histologically non-malignant breast tissues were seeded within type I collagen gels in serum-free medium, they successively grew and protruded many radial duct-like extensions with lumina. Separate deletion of each of the supplements from the medium showed that growth as well as morphological differentiation of carcinoma-derived cells were prevented in the absence of epidermal growth factor (EGF) or hydrocortisone. Removal of insulin or ethanolamine plus phosphoethanolamine caused a significant inhibition of cell growth without interfering with the morphological differentiation. Contrary to the case with carcinoma-derived cells, both growth and morphological differentiation of epithelial cells derived from non-malignant breast tissues were prevented when EGF, hydrocortisone or insulin was absent. Removal of each of the other supplements (except for transferrin), including ethanolamine plus phosphoethanolamine, prolactin, or prostaglandin, caused a significant inhibition of cell growth with no apparent inhibition of morphological differentiation. The present results suggest that human epithelial cells derived from either carcinoma or histologically non-malignant breast tissues strongly depend on the presence of EGF and hydrocortisone and there is a decreased dependence on insulin in carcinoma-derived cells with respect to their growth and morphological differentiation during culture within collagen gels.